Bioequivalence and Bioavailability Forum

Hi Helmut,

What I was trying to say is:

FDA guidance shows:
Sequence 1=TRR
Sequence 2=RTR
Sequence 3=RRT

CRO used the following:
Sequence 1=BAB (RTR)
Sequence 2=ABB (TRR)
Sequence 3=BBA (RRT)

When you look at the SAS code from the Progesterone guidance for 3-way partial replicate. The section where you generate 3 datasets, 1 for test, 1 for ref1 and 1 for ref2.

Dataset containing TEST observations:
data test;
set pk;
if trt='T';
latt=lauct;
run;
Dataset containing REFERENCE 1 observations:
data ref1;
set ref;
* if (seq=1 and per=2) or (seq=2 and per=1) or (seq=3 and per=1); *
lat1r=lauct;
run;
Dataset containing REFERENCE 2 observations:
data ref2;
set ref;
* if (seq=1 and per=3) or (seq=2 and per=3) or (seq=3 and per=2); *
lat2r=lauct;
run;

See the if statements in astericks? Those statements should be written according to the way the sequences were set up (i.e., the aboves were written based on how FDA set up the sequences meaning Sequence 1 = TRR, Sequence 2 = RTR, Sequence 3 = RRT). My suspicion is that the CRO failed to update those statements according to the way they set up their sequences but instead they used the FDA codes (if statements) above. How did I find out? I used the above codes AS IS with the CRO data and I ended up with the same SCABE results. However, when I set up the if statements the way they are supposed to be as per CRO's sequences (Sequence 1 = BAB, Sequence 2 = ABB, Sequence 3 = BBA) then the results were different.

As I go further down the SAS code, the PROC GLM analysis for dlat (below). Would incorrect sequence assignment leads to different results (Perhaps d_labes or ElMaestro can help since they use SAS?)

Intermediate analysis - dlat
proc glm data=scavbe;
class seq;
model dlat=seq;
ods output overallanova=dglm1;
ods output NObs=dglm3;
title1 'scaled average BE';
run;

Can I post the data up (of course no labels)? 72 subjects though. Just Cmax.

I hope I am wrong but I can't confirm so need a 2nd pair of hands.

Thanks
John